evobrutinib   Click here for help

GtoPdb Ligand ID: 9752

Synonyms: A250 [WO2012170976] | M-2951 | M2951 | MSC 2364447 | MSC-2364447C | MSC2364447C
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Evobrutinib is a Bruton's tyrosine kinase Inhibitor discovered by Merck, that has clinical potential across multiple autoimmune conditions (including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis) [1]. it is an orally active, ootent, and highly selective inhibitor with a covalent binding mode. The chemical structure is claimed as A250 in patent WO2012170976 [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 93.37
Molecular weight 429.22
XLogP 4.11
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
Isomeric SMILES C=CC(=O)N1CCC(CC1)CNc1ncnc(c1c1ccc(cc1)Oc1ccccc1)N
InChI InChI=1S/C25H27N5O2/c1-2-22(31)30-14-12-18(13-15-30)16-27-25-23(24(26)28-17-29-25)19-8-10-21(11-9-19)32-20-6-4-3-5-7-20/h2-11,17-18H,1,12-16H2,(H3,26,27,28,29)
InChI Key QUIWHXQETADMGN-UHFFFAOYSA-N
Immunopharmacology Comments
Evobrutinib is a selective BTK inhibitor that potently inhibits B cell receptor- and Fc receptor-mediated signaling and downstream activation/function of human B cells and innate immune cells (e.g. monocytes and basophils). It has therapeutic potential for the management of B cell-driven autoimmune conditions [2].
Immunopharmacology Disease
Disease X-Refs Comment References
Rheumatoid arthritis Disease Ontology: DOID:7148
OMIM: 180300
Phase 2 clinical candidate for RA- see NCT03233230
Systemic lupus erythematosus Disease Ontology: DOID:9074
OMIM: 152700
Orphanet: ORPHA536
Phase 2 clinical candidate for SLE- see NCT02975336
Relapsing-remitting multiple sclerosis Disease Ontology: DOID:2378
Phase 3 clinical candidate for RR-MS- see NCT04032171 and NCT04032158. Positive Phase 2 results (from NCT02975349) are reported in Montalban et al., 2019. In this study once daily evobrutinib (75 mg) reduced the number of gadolinium-enhancing lesions significantly more than placebo. 4